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NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast

AuthorsJiménez-Hidalgo, María ; Santos-Ocaña, Carlos ; Padilla, Sergio; Villalba, José M.; López-Lluch, Guillermo ; Martín-Montalvo, Alejandro ; Minor, Robin K.; Sinclair, David A.; Cabo, Rafael de; Navas, Plácido
KeywordsChronological lifespan
Coenzyme Q
Coencyme Q reductase
Dietary restriction
Plasma membrane
Replicative lifespan
Cell aging
Electron transport complex
Energy metabolism
Histone Deacetylases
Saccharomyces cerevisiae
Issue Date23-Feb-2009
PublisherBlackwell Publishing
CitationAging Cell 8(2): 140-151 (2009)
AbstractThe activity and expression of plasma membrane NADH coenzyme Q reductase is increased by calorie restriction (CR) in rodents. Although this effect is well-established and is necessary for CR's ability to delay aging, the mechanism is unknown. Here we show that the Saccharomyces cerevisiae homolog, NADH-Coenzyme Q reductase 1 (NQR1), resides at the plasma membrane and when overexpressed extends both replicative and chronological lifespan. We show that NQR1 extends replicative lifespan in a SIR2-dependent manner by shifting cells towards respiratory metabolism. Chronological lifespan extension, in contrast, occurs via an SIR2-independent decrease in ethanol production. We conclude that NQR1 is a key mediator of lifespan extension by CR through its effects on yeast metabolism and discuss how these findings could suggest a function for this protein in lifespan extension in mammals.
Description22 páginas, 8 figuras.
Publisher version (URL)http://dx.doi.org/10.1111/j.1474-9726.2009.00461.x
Appears in Collections:(CABD) Artículos
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